Table 2.
Evaluating statistical interaction effects (epistasis) between IL4R SNPs and FLG variants on the risk of allergic sensitization: results from IOW cohort study via longitudinal analyses.
| IL4R SNPs | Genetic Model† | Genotype† | Interaction term (IL4R × FLG)‡ |
|---|---|---|---|
| P value | |||
| rs8832 | Additive | GG/AG/AA | 0.791 |
| rs1110470 | Additive | GG/AG/AA | 0.388 |
| rs1805011 | Heterosis | AA/CC vs. AC | 0.389 |
| rs1805012 | Dominant | GG/AG vs. AA | 0.929 |
| rs2057768 | Additive | GG/AG/AA | 0.412 |
| rs3024604 | Heterosis | AA/GG vs. AG | 0.891 |
| rs3024676 | Heterosis | AA/CC vs. AC | 0.003 * |
| rs3024685 | Additive | GG/AG/AA | 0.703 |
| rs4787423 | Recessive | GG vs. AA/AG | 0.649 |
| rs6498012 | Additive | GG/CG/CC | 0.878 |
| rs12102586 | Recessive | AA vs. AG/GG | 0.845 |
| rs16976728 | Dominant | AA/AG vs. GG | 0.809 |
SNP: Single nucleotide polymorphism.
*FDR corrected P value = 0.036.
†For each IL4R SNP the best fitting genetic risk model (dominant, recessive, heterosis, or additive) was selected as detailed in the ‘Methods’ section. Under the additive model, the three genotypes were coded and entered in the regression model in a dosage-effect manner (from smaller to larger effect). For instance, the best fitting genetic risk model for SNP rs8832 is ‘additive’ model, meaning that the risk of allergic sensitization increases gradually from least risk among those with GG genotype to moderate risk among those with AG genotype to highest risk among those with AA genotype. In the ‘heterosis’ model we collapsed the two homozygote genotypes together and compare their risk to the heterozygote risk. For example, the best fitting genetic risk model for SNP rs1805011 is ‘heterosis’ model, in which the risk of homozygote genotypes (AA/CC) was compared to the risk of heterozygote genotype (AC). For SNP rs1805012, in the dominant model we compared the risk of variant homozygote and heterozygote (GG/AG) genotypes to the risk of wild-type homozygote (AA) genotype. For SNP rs4787423, in the recessive model we compared the risk of variant homozygote (GG) genotype to the risk of wild-type homozygote and heterozygote (AA/AG) genotypes.
‡Interaction term refers to the product term that we included in the regression model to test for the presence of multiplicative statistical interaction between FLG variants and IL4R SNPs. Since there are 12 IL4R SNPs, we tested 12 interaction terms (IL4R SNP × FLG variants), while using the best fitting genetic risk model for each IL4R SNP.